Establishment of method for identification of ubiquitinated protein

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19506
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical structure and function and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Hatakeyama Shigetsugu 北海道大学, 医学研究院, 教授 (70294973)
• Research Collaborator: TAKAHASHI Hidehisa 横浜市立大学, 医学研究科, 教授 (20399819) ; WATANABE Masashi 北海道大学, 医学研究院, 講師 (10632424)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: ユビキチン / TRIM型E3 / TUBE / Parkin

Outline of Final Research Achievements

Ubiquitination is a chemical modification that controls protein degradation and is one of the most important post-translational modifications that support many biological phenomena. The reaction system is mediated by ubiquitin ligases (E3) selectively recognizing substrate proteins. Therefore, it is important to identify specific substrates of each E3 and to determine the ubiquitination site of substrate proteins in understanding the biological phenomenon that they are associated with. However, due to various problems, it is still far from standardizing ubiquitinated substrate identification methods. In this study, we challenged to establish a novel technology using TUBE (artificial protein exhibiting high affinity binding to polyubiquitin chain) and ubiquitin remnant antibody allows comprehensive application to various types of ubiquitin ligase (E3) and the E3-substrates relationship was analyzed.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

本申請で開発した基質同定法は、これまでの問題点を原理的に解消した全く新しい手法であり、すべてのE3に対して適用可能であるため、E3の機能解析が加速することが期待できると思われる。本手法の応用により、正常及び異常（疾患）に関与しているユビキチン化修飾の全貌解明が期待できる。したがって、将来的には疾患特異的ユビキチン化部位を標的とした創薬のシーズを発掘できる可能性がある。